Current artificial lungs fail in 1-4 weeks due to surface-induced thrombosis. Biomaterial coatings may be applied to anticoagulate artificial surfaces, but none have shown marked long-term effectiveness. Poly-carboxybetaine (pCB) coatings have shown promising results in reducing protein and platelet-fouling in vitro. However, in vivo hemocompatibility remains to be investigated. Thus, three different pCB-grafting approaches to artificial lung surfaces were first investigated: 1) graft-to approach using 3,4-dihydroxyphenylalanine (DOPA) conjugated with pCB (DOPA-pCB); 2) graft-from approach using the Activators ReGenerated by Electron Transfer method of atom transfer radical polymerization (ARGET-ATRP); and 3) graft-to approach using pCB randomly copolymerized with hydrophobic moieties. One device coated with each of these methods and one uncoated device were attached in parallel within a veno-venous sheep extracorporeal circuit with no continuous anticoagulation (N=5 circuits). The DOPA-pCB approach showed the least increase in blood flow resistance and the lowest incidence of device failure over 36-hours. Next, we further investigated the impact of tip-to-tip DOPA-pCB coating in a 4-hour rabbit study with veno-venous micro-artificial lung circuit at a higher activated clotting time of 220-300s (N≥5). Here, DOPA-pCB reduced fibrin formation (p=0.06) and gross thrombus formation by 59% (p<0.05). Therefore, DOPA-pCB is a promising material for improving the anticoagulation of artificial lungs.

Background and study aims Endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (ERCP) (EDGE) is a novel technique for managing pancreaticobiliary diseases in patients with a history of Roux-en-Y Gastric Bypass (RYGB). It has shown to have high technical success rates and fewer adverse events as compared to laparoscopic-assisted ERCP (LA-ERCP). We compared the technical success and clinical outcomes of EDGE vs. LA-ERCP vs. E-ERCP. Patients and methods A retrospective chart review was performed for 56 patients, of whom 18 underwent LA-ERCP, 12 underwent E-ERCP, and 26 had EDGE, and a comparison of technical success and complication rates was done. Results Baseline demographic characteristics of patients undergoing these procedures, including age and gender, were comparable. The technical success rate for patients in the EDGE group were 100 % (n = 26), compared with 94 % (n = 17) and 75 % (n = 9) in the LA-ERCP and E-ERCP groups (P = 0.02). In the EDGE group, 8 % of patients (n = 2) had bleeding, and 4 % of patients (n = 1) had lumen-apposing metal stent migration occur during the procedure. In the LA-ERCP group 6 % (n = 1) of patient had bleeding, 6 % (n = 1) post-ERCP pancreatitis and 6 % (n = 1) were diagnosed with an intra-abdominal infection post-procedure. Time to complete the EDGE procedure was significantly shorter at 79 ± 31 mins, compared with 158 ± 50 mins for LA-ERCP and 102 ± 43 mins for E-ERCP (P < 0.001). Conclusion EDGE is a novel procedure with short procedure times and an effective alternative to LA-ERCP and E-ERCP in management of pancreaticobiliary diseases in patients with a history of RYGB.

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Invasive lobular breast carcinoma (ILC), one of the major breast cancer histological subtypes, exhibits unique clinical and molecular features compared to the other well-studied ductal cancer subtype (IDC). The pathognomonic feature of ILC is loss of E-cadherin, mainly caused by inactivating mutations within the CDH1 gene, but the extent of contribution of this genetic alteration to ILC-specific molecular characteristics remains largely understudied. To profile these features transcriptionally, we conducted single cell RNA sequencing on a panel of IDC and ILC cell lines, as well as an IDC cell line (T47D) with CRISPR-Cas9-mediated knock out (KO) of CDH1. Inspection of intra-cell line heterogeneity illustrated genetically and transcriptionally distinct subpopulations in multiple cell lines and highlighted rare populations of MCF7 cells highly expressing an apoptosis-related signature, positively correlated with a pre-adaptation signature to estrogen deprivation. Investigation of CDH1 KO-induced alterations showed transcriptomic membranous systems remodeling, elevated resemblance to ILCs in regulon activation, and suggests IRF1 as a potential mediator of reduced proliferation and increased cytokine-mediated immune-reactivity in ILCs..

Breast cancer, the most common type of cancer affecting women, encompasses a collection of histologic (mainly ductal and lobular) and molecular subtypes exhibiting diverse clinical presentation, disease trajectories, treatment options, and outcomes. Immunotherapy has revolutionized treatment for some solid tumors but has shown limited promise for breast cancers. In this review, we summarize recent advances in our understanding of the complex interactions between tumor and immune cells in subtypes of breast cancer at the cellular and microenvironmental levels. We aim to provide a perspective on opportunities for future immunotherapy agents tailored to specific features of each subtype of breast cancer. Significance: Although there are currently over 200 ongoing clinical trials testing immunotherapeutics, such as immune-checkpoint blockade agents, these are largely restricted to the triple-negative and HER2+ subtypes and primarily focus on T cells. With the rapid expansion of new in vitro, in vivo, and clinical data, it is critical to identify and highlight the challenges and opportunities unique for each breast cancer subtype to drive the next generation of treatments that harness the immune system.

Background There is increasing interest in better understanding the biology and clinical presentation of invasive lobular cancer (ILC), which is the most common special histological subtype of breast cancer. Limited large contemporary data sets are available allowing comparison of clinicopathologic features between ILC and invasive ductal cancer (IDC). Methods The Great Lakes Breast Cancer Consortium was formed to compare clinical behavior of ILC (n = 3617) and IDC (n = 30 045) from 33 662 patients treated between 1990 and 2017 at 3 large clinical centers. We used Kaplan-Meier analysis, Cox proportional hazards modeling, and propensity score matching to evaluate treatment differences and outcomes. All statistical testing used 2-sided P values. Results Compared with IDC, patients with ILC were more frequently diagnosed at later stages and with more lymph node involvement (corrected P &lt; .001). Estrogen receptor–positive ILCs were of lower grade (grade 1 and 2: 90% in ILC vs 72% in IDC) but larger in size (T3 and 4: 14.3% in ILC vs 3.4% in IDC) (corrected P &lt; .001), and since 1990, the mean ILC size detected at diagnosis increased yearly. Patients with estrogen receptor (ER)–positive ILC underwent statistically significantly more mastectomies compared with ER-positive IDC (57% vs 46%). Using Kaplan-Meier analysis, patients with ER-positive ILC had statistically significantly worse disease-free survival and overall survival than ER-positive IDC although 6 times more IDCs were classified as high risk by OncotypeDx Breast Recurrence Score assay. Conclusions This large, retrospective, collaborative analysis with 3 clinical centers identified meaningful differences in clinicopathological features between ILC and IDC, providing further evidence that these are 2 different entities requiring different clinical management.

Objectives The aim of this study was to evaluate depression in pancreatic cancer (PC) patients before and after a cancer diagnosis using a US-based healthcare database. We also sought to study the impact of treatment of depression in PC patients on all-cause mortality. Methods Pancreatic cancer patients with comorbid depression in Explorys (1999–2019) were compared with controls using odds ratios with 95% confidence intervals. Rates of depression diagnosed within 6 months, 1 year, and 3 years before and after a PC diagnosis were recorded. Patients who developed depression after a PC diagnosis were further categorized into those treated for depression using mental health professionals (MHPs), pharmacologic treatment, or both (2015–2019). Results Of the 62,450 PC patients, 10,220 (16.4%) were diagnosed with depression before PC and 8130 (13%) were diagnosed with depression after PC. Patients diagnosed with depression after PC had a significantly higher all-cause mortality than patients with PC alone (P < 0.0001). Involvement of MHP significantly improved all-cause mortality (P = 0.0041). Conclusions Most post-PC depression is diagnosed in the first 6 months after a PC diagnosis. Although depression significantly increases PC mortality, integrating MHP in the care of PC patients with depression improves outcomes.

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